Genetik der Fettlebererkrankung

Alcoholic and non-alcoholic fatty liver diseases are the most common chronic liver disorders world-wide, especially in developed countries; however, the predominant risk factors, namely obesity, metabolic syndrome and chronic alcohol abuse, only lead to steatohepatitis and liver cirrhosis in the minority of patients. Thus, additional, possibly genetic risk factors may predispose to manifestation and progression of disease, a notion well supported by epidemiological data for both entities. Both phenotypes thus constitute complex diseases where environmental factors, behavior and genetic risk factors interact to determine disease risk and characteristics. As a result of initial genetic studies a robust susceptibility gene PNPLA3 (patatin-like phospholipase domain-containing 3) has been identified and confirmed for both disorders. Homozygous carriers of the risk variant PNPLA3-148M have an approximately ?4-fold increased risk of non-alcoholic steatohepatitis and a ?6-fold increased risk of alcoholic liver cirrhosis. Potentially, the relatively high risk conferred by this variant may be used for future prevention and risk stratification strategies.